An experimental stroke preventer from Bayer and Johnson & Johnson is likely to win a recommendation from U.S. health advisers next week, but not without concern over risks seen when patients come off the drug.
A key issue for the Food and Drug Administration advisers may be the so-called rebound effect of the medicine Xarelto. When patients stopped taking it and resumed older drug warfarin, higher risk of stroke was seen in trials.
"We think the FDA advisory panel will be concerned that there's a 'rebound' effect with discontinuing Xarelto," Wells Fargo analysts said in a research note on Thursday. "However, our consultants do not believe this will be a deal breaker."
Xarelto's shortcomings may also relegate it to second place in the marketplace behind a rival treatment being developed by Bristol-Myers Squibb Co. and Pfizer Inc., in an anti-clotting market that could top $10 billion a year, analysts say.
The advisory panel is set to consider the data on Xarelto next Thursday, after the FDA releases its initial findings on the drug on Tuesday.
"Key opinion leaders expect a panel recommendation for Xarelto, but not without controversy," analysts at Leerink Swann wrote in a note Thursday.
The FDA usually follows the advice of its advisory panels, and Xarelto could be approved by November if the pill wins support at the meeting.
Xarelto is one of several promising entrants angling to replace risky clot preventer warfarin for people with dangerously irregular heart rhythms, called atrial fibrillation (AF).
AF patients' irregular heartbeats can cause blood to pool, increasing their risk of blood clots and strokes. But many are unwilling to take warfarin, which requires regular blood tests, or are unable to tolerate the old medicine.
Boehringer Ingelheim's Pradaxa is already approved in stroke prevention, while Eliquis, from Bristol-Myers and Pfizer, has so far shown the best clinical data, especially for reducing the risk of major bleeding.
RANKING THE COMPETITION
Jeff Jonas, an analyst with Gabelli & Co., predicted the advisory panel will recommend Xarelto because of its effectiveness and acceptable bleeding risk, and its advantages over warfarin.
"Xarelto will be overshadowed by apixaban (Eliquis), but it is going to be a decent drug and could generate $1 billion to $2 billion in annual sales, with the marketing muscle of J&J and Bayer," he said. Bristol and Pfizer plan to submit Eliquis for U.S. approval later this year for preventing stroke.
Another issue is some inconsistent data. A clinical trial last November showed Xarelto, known generically as rivaroxaban, was 21 percent better at preventing stroke in patients with AF compared with warfarin.
But when all those who entered the trial were evaluated, no superiority was established for Xarelto, a fact that is likely to come up in panel discussions.
"A superiority claim over warfarin ... is unlikely in our view and is not widely anticipated," said Barbara Ryan, analyst at Deutsche Bank, in a research note on Friday.
Panelists may also focus on the fact that warfarin was not used as effectively as it might have been in the study, making it more difficult to compare it with Xarelto.
Xarelto's advantage over rivals may come in its dosing, since it needs to be taken only once a day as opposed to twice for Eliquis and Pradaxa, a key factor for elderly patients taking multiple medications.
Gabelli & Co.'s Jonas said Eliquis is likely to capture 50 percent or more of the warfarin-replacement market, with Xarelto in second place comfortably ahead of Pradaxa.
"Pradaxa is being dismissed; it will be relatively small," he predicted.
Even though Pradaxa was the first to market, having been approved by U.S. regulators last year, it causes gastrointestinal side effects in a significant percentage of patients and has special storage requirements.
Pradaxa works by directly blocking a protein called thrombin that plays a key role in the clotting process, while Eliquis and Xarelto block the Factor Xa protein.
The three medicines — and a fourth from Daiichi-Sankyo called edoxaban that is due to report pivotal results in 2012 — will greatly expand the number of patients with AF taking anticoagulants.
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